The objectives of this project are to: a) develop an experimental model for the study of mechanical and electrical effects on bone remodeling, b) delineate some early biochemical cellular events evoked by these stimuli and relate them to subsequent tissue changes, c) use this approach to search for the optimal combination of mechanical, electrical and pharmacological means for clinical application. The methods employed will include quantitative application of mechanical pressure and/or electric fields to long bones (organ explants) and cells in culture. Cyclic nucleotide accumulation, DNA replication and glucose utilization will be measured. In addition, histologic, autoradiographic, morphometric and vital staining methods will be used to examine cellular (cell division, cell migration, cytodifferentiation) and tissue changes, which will be related to the molecular events. The accumulated knowledge should lead to the efficient utilization of mechanical and electrical techniques in the treatment of hard tissue problems including: craniofacial anomalies, periodontal disease, bone fractures and other related disorders.